JPWO2002076240A1 - Health food containing nattokinase and fermented milk products - Google Patents
Health food containing nattokinase and fermented milk products Download PDFInfo
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- JPWO2002076240A1 JPWO2002076240A1 JP2002574765A JP2002574765A JPWO2002076240A1 JP WO2002076240 A1 JPWO2002076240 A1 JP WO2002076240A1 JP 2002574765 A JP2002574765 A JP 2002574765A JP 2002574765 A JP2002574765 A JP 2002574765A JP WO2002076240 A1 JPWO2002076240 A1 JP WO2002076240A1
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Abstract
本発明は、納豆の成分であるナットウキナーゼを容易に摂取し得る食品組成物を提供する。また、本発明は、それぞれ苦手な人がいる和風食材の納豆と洋風食材の乳発酵産物とを組み合わせ、誰でもその保健効果を享受でき、かつ特異な保健効果を期待することができる食品組成物を提供する。本発明は、凍結乾燥した乳発酵産物、ナットウキナーゼ、及び食品に使用可能な担体を含有してなる食品組成物に関する。さらに、本発明は、これらの成分を含有した抗血栓作用、血液流動性向上作用、血小板凝集抑制作用、及び脂質代謝改善作用を有する機能性食品に関する。本発明の食品組成物は、納豆特有の臭いもなく、容易に乳発酵産物と納豆の成分を摂取することができるだけでなく、乳発酵産物由来の整腸作用・免疫賦活作用・抗腫瘍活性に加えて、納豆のナットウキナーゼとの相乗作用による血栓症の治療と予防効果などの保健効果が期待される。The present invention provides a food composition that can easily ingest nattokinase, a component of natto. Further, the present invention combines a natto of Japanese-style ingredients and a milk-fermented product of Western-style ingredients, each of which has a weak person, so that anyone can enjoy the health effects thereof and can expect a unique health effect. I will provide a. The present invention relates to a food composition comprising a freeze-dried milk fermentation product, nattokinase, and a carrier usable for food. Furthermore, the present invention relates to a functional food containing these components, which has an antithrombotic effect, a blood fluidity improving effect, a platelet aggregation suppressing effect, and a lipid metabolism improving effect. The food composition of the present invention has no odor peculiar to natto, can easily ingest the components of dairy fermentation products and natto, and has an intestinal action, an immunostimulatory effect, and an antitumor activity derived from dairy fermentation products. In addition, health effects such as treatment and prevention of thrombosis due to the synergistic effect of natto with nattokinase are expected.
Description
技術分野
本発明は、日本の食生活に古くから入り込んでいる納豆に由来する健康食品に関する。より詳細には、その保健効果が注目されている獣乳発酵産物と日本の食生活に古くから取り入れられている納豆に由来するナットウキナーゼを含有してなる食品組成物に関し、特に抗血栓作用、血液流動性向上作用、血小板凝集抑制作用、及び脂質代謝改善作用を有し、血栓症の治療と予防に優れた効果が期待される機能性食品に関する。
背景技術
近年、健康に対する関心の高まりから、食品が従来持っている生命を維持するための栄養素という一次機能及び味覚という二次機能に加え、三次機能である生体のリズム調節、生体防御、疾病予防と回復、老化防止などの健康を維持する体調調節機能に対しても、種々の研究が進められている。そして、対症療法的な治療を目的とした医薬品とは別に、三次機能を高めた、より積極的に健康を維持するための健康食品又は機能性食品を日常生活に取り入れることは、健康に対する関心の高まりと共に医療費の増加抑制などの期待から、広く注目されてきている。特に、生活様式の多様化、食生活の変化などから、このような健康食品又は機能性食品が有する生活習慣病及び各種慢性病に対する予防効果について、様々な分野からのさらなる研究が必要とされている。
機能性食品とは、一般に、通常の食品等を素材及び成分として新しい技術により製造され、日常的に摂取可能な、健康食品よりもさらに特定の保健効果を持たせた食品とされている。例としては、虫歯になりにくい甘味料を使用した食品などが市場に出ている。これらは特別に調製の必要な原料及び素材ではなく、日常摂取していたり、伝統的に利用している食品から、多くが開発製造されている。
このような状況の下、健康食品又は機能性食品は幅広いニーズを有しており、より具体的な効能が求められてもいる。
例えば、機能性食品に対して「血液をサラサラにする効果」と一般に言われている血液流動性向上効果を求める傾向が見られる。血液の流動性を支配する因子には、血管系の問題と血液成分の機能が関係している。血管の内径が動脈硬化で狭くなれば血流が悪くなり、また、血液中の脂質レベルが高くなれば血液粘度が上昇し、さらに血小板凝集能が冗進し、血管内血栓形成の際には血栓溶解能が低下し、血流が悪くなる。また、血球成分においては毛細血管よりも直径の大きい赤血球が毛細血管を通過するには、自身の形を柔軟に変えて血管内皮細胞に酸素を与え、Ｃｏ２を受け取り、静脈を通じて肺へと循環している。このような赤血球の柔軟性を赤血球変形能といい、この機能は生活習慣病や慢性病、ストレスなどによって悪化し、微小循環機能が低下する。
具体的な食品例を挙げると、納豆は、我が国に古くから愛用されてきた食品であり、枯草菌の１種として分類される納豆菌（Ｂａｃｉｌｌｕｓ ｓｕｂｔｉｌｉｓ ｎａｔｔｏ）による発酵食品である。日本の伝統的な健康食品として、欧米にも「野菜のチーズ（ｖｅｇｅｔａｂｌｅ ｃｈｅｅｓ）」などと紹介されている。近年になって、納豆にはナットウキナーゼ〔納豆キナーゼ（ｎａｔｔｏｋｉｎａｓｅ）〕という酵素が含有されていることが報告されてきた。このナットウキナーゼは、納豆から抽出・塩析・クロマトグラフィー・ゲル濾過等の操作を組合せることによって容易に精製され、白色結晶性粉末で、納豆臭があり、水溶液は無色透明で、ｐＨ６〜１２の塩基性水溶液中では６０℃までの加熱に対して安定であることが知られている。また、そのアミノ酸配列も決定され、Ｓ−Ｓ結合を全く持たない２７５個のアミノ酸残基からなる１本鎖構造のポリペプチドであることが分かっている。そのゲル濾過による分子量は、２０，０００±５，０００である。
また、持続性においても、ナットウキナーゼは４〜１２時間という作用時間を有し、これはウロキナーゼと比較すると長いものである。
納豆に含まれるこのナットウキナーゼが納豆の独特の食感を呈するのみならず、この酵素は血栓溶解酵素であるウロキナーゼ、組織プラスミノーゲンアクチベーター（ＴＰＡ）等と同じセリンプロテアーゼ系の酵素であり、それ自身強力な血栓溶解能を有すると共に、血中のＴＰＡ量を増加させる間接的効果も確認されている。
このようにナットウキナーゼの有する健康上の好ましい作用については種々報告されてきているが、ナットウキナーゼには納豆独特の臭いがあり、これをそのまま含有させて食品として使用するには、食感上で多くの問題があった。
また、ヨーグルト、チーズなどの獣乳発酵産物は、その食品が有する保健効果への関心の高まりによって消費量が増えてきており、獣乳発酵産物をベースにした菓子等の多様な食品類が開発されてきている。特に獣乳発酵産物を多量に摂取する民族に長生きをするヒトが多いことや、癌などの発病率が低いことなどが報告されてきており、健康食品としての獣乳発酵産物が注目されてきた。また、近年では、血圧降下作用を有することも判ってきている。
しかし、元来、米食基本の食生活を有する日本人、とりわけ高齢者にとっては、本質的になじみにくい食材である。
発明の開示
本発明は、それぞれ保健効果が注目されているが、依然苦手な人がいる乳発酵産物と納豆を組み合わせて、高齢者でも若者でも、どの地方の誰でもが、容易に摂取が可能で、それらの保健効果を享受できるような食品組成物を提供するものである。
また、本発明は、ナットウキナーゼの有する特有の臭いや味を改善することにより、ナットウキナーゼを容易に摂取することができるようにした食品組成物を提供するものである。
本発明者らは、納豆の作用効果と獣乳発酵産物の作用効果とを併せ持つ健康食品を検討していたところ、和風食材の納豆と洋風食材の獣乳発酵産物の両者を含有した食品組成物が意外にもナットウキナーゼが有する特有の臭いや味を改善すると共に、両者の作用効果を充分に引き出すことができる食品となりうることを見出した。
即ち、本発明は、凍結乾燥した乳発酵産物、ナットウキナーゼ、及び食品に使用可能な担体を含有してなる食品組成物に関する。また、本発明は、凍結乾燥した乳発酵産物、及びナットウキナーゼに、さらにホスファチジルセリン、高麗人参加工品などからなる補助成分を含有させてなる食品組成物に関する。さらに、本発明は、これら成分を含有した抗血栓作用、血液流動性向上作用、血小板凝集抑制作用、及び脂質代謝改善作用を有する機能性食品に関する。
発明を実施するための最良の形態
本発明の食品組成物における凍結乾燥した乳発酵産物とは、獣乳すなわち牛、馬、羊、山羊などの乳を発酵させて出来るケフィア、ヨーグルト、クーミス、ラッシーなどの凍結乾燥品であり、当該分野において知られている方法によって製造することができる。好ましくは、牛乳へのケフィア・グレインの添加、発酵によって得られる産物であるケフィアの凍結乾燥品であり（以下、ケフィアと略記する）、その製造方法については、例えば特開昭６２−８３８４２号などを参照することができ、その形状は白色〜淡黄白色粉末状である。
次に、本発明におけるナットウキナーゼ（納豆キナーゼ：ｎａｔｔｏｋｉｎａｓｅ）について説明する。このナットウキナーゼは、我が国古来の大豆発酵食品であるナットウ（納豆）から抽出、塩析、クロマトグラフィー、ゲル濾過等の操作の組合せによって容易に製造され、市販品も知られている。白色結晶性粉末、納豆臭があり、水溶液は無色透明で、ｐＨ６〜１２の塩基性水溶液中では６０℃までの加熱に対して安定である。血栓溶解酵素であるウロキナーゼ、組織プラスミノーゲンアクチベーター（ＴＰＡ）等と同じセリン酵素であり、そのアミノ酸配列も決定され、Ｓ−Ｓ結合を全く持たない２７５個残基からなる１本鎖構造のポリペプチドであることが特徴的である。ゲル濾過による分子量は２０，０００±５，０００であり、平均的な活性は約４０ＣＵ（プラスミン単位）／ｇである。そして、強力な血栓溶解能を有すると共に、血中のＴＰＡ量を増加させる間接的効果も確認されている。ナットウキナーゼは安価である上に、その作用の持続性が長時間であり、さらに、最近ではＯ−１５７のような感染症に対する有効性も注目されている。
本発明のナットウキナーゼとしては、市販のナットウキナーゼをそのまま使用することができ、必ずしも充分に精製されたナットウキナーゼを使用する必要はなく、ナットウキナーゼを含有しているものであって食品として使用できるものであれば特に制限はない。例えば、納豆抽出物またはその加工品のようなナットウキナーゼを含有するものであれば、本発明のナットウキナーゼとして使用することができる。
本発明の食品組成物における担体は、食品に使用可能で、本発明の食品組成物の風味に格別の悪影響を与えるものでなく、ナットウキナーゼや乳発酵産物の保健上の作用効果に好ましい影響を与えるものであれば特に制限はない。
本発明の食品組成物における補助成分は、食品として使用される食材又はそのエキスなどであって、本発明の健康食品の風味に格別の悪影響を与えるものでなく、ナットウキナーゼや乳発酵産物の保健上の作用効果に好ましい影響を与えるものであれば特に制限はない。好ましい補助成分としては、ホスファチジルセリンなどのリン脂質、高麗人参などが挙げられる。
ホスファチジルセリン（ＰＳ）はリン脂質の一種であり、初期のアルツハイマー病や加齢による記憶力低下に対して学習能力、記憶力、思考力、認識力などの脳の機能を高める事ができるとされており、他にパーキンソン病やうつ病への改善効果も期待されている。すなわちＰＳは細胞内への栄養の取り込みを促進し、神経細胞間の情報伝達を活性化し、神経伝達物質の生成を促進する作用を有すると考えられ、アルツハイマー型痴呆の治療への効果が期待される。
高麗人参は、古くから健康食品や漢方薬の成分として知られているものであり、血糖降下作用、副腎皮質機能の改善、心筋機能の改善、新陳代謝の改善、コレステロールの改善などの作用を有することが知られている。高麗人参しては、高麗人参加工品、例えばその抽出物、乾燥品、散剤などを使用することができる。
さらに、本発明の食品組成物における他の好ましい補助成分として、食品として使用される食材又はそのエキスである、各種ビタミン、カルシウム剤、乳酸菌、オリゴ糖、食物繊維、ムメフラール含有梅エキス、黒酢などが挙げられる。
オリゴ糖はグルコース、フラクトースあるいはガラクトースなどの単糖類が２〜１０個グリコシド結合したものであり、すでに市販品が知られており、腸内の有用菌であるビフィズス菌や乳酸菌などの乳酸菌類やフェカリス菌の栄養分となる増殖因子である。従って腸内有用菌が増殖し、有用菌優勢の好ましい腸内環境をつくることができる。
食物繊維は、おから、干ししいたけ、干しひじき、きくらげ、海苔、大豆などの植物性食品に多く含まれている繊維質である。これらの成分は古くは栄養分の消化及び吸収を妨げ、エネルギー源にならない不消化成分として軽視されていたが、近年では整腸効果及び便通改善などの点で注目されている。
有胞子乳酸菌は安定性が高く、乳酸菌生成能力も優れているので、確実に腸管に到達し、活発な整腸作用が見込まれる。カルシウム剤はカルシウム補強作用を、複合ビタミン剤は特定ビタミン強化の作用を有する。
ムメフラール含有梅エキスは、古くから薬効が認められており、疲労回復、抗菌、消炎、消化器官の活性化などの作用を有することが知られている。その含有成分は、ミネラル、カテキン、アミノ酸などと多様である。近年、特に、生梅から梅エキスを製造する過程おいて含有成分を加熱することにより生成されるムメフラールが、血小板凝集を阻害する作用を有することが見いだされ、梅エキスに含有される他の成分との相乗効果による血流改善効果が注目されている。
黒酢は、米から製造される酢の１種であり、コレステロールや中性脂肪の改善（脂質代謝改善作用）、血液流の改善（赤血球変形能改善作用）、抗アレルギー作用、血圧降下作用、血糖降下作用、肝臓活性化作用、抗酸化作用などを有することが知られている。ただし、ナットウキナーゼの有する保健効果を充分に享受できるように、食品組成物に含有させる際に予めマイクロカプセル化するなどの加工を施すことが好ましい。黒酢としては、米麹、蒸米、及び地下水を原料とし、糖化、アルコール発酵、及び酢酸発酵の３つの発酵が自然に進行した黒酢が好ましい。
さらにまた、次のような食品として使用される食材又はそのエキスも、本発明の食品組成物における補助成分として、挙げることができる。すなわち、繊維素溶解活性作用及び脂質低下作用を有するタマネギエキス、血流改善作用を有するピーマン及びピーナツ、血流改善作用を有するイチョウ葉及びトマト、抗酸化作用及び心臓疾患予防作用を有するＣｏＱ１０（補酵素Ｑ１０）、抗酸化作用を有するアスタキサンチン、抗酸化作用及び動脈硬化改善作用を有するトコトリエノール、心臓疾患予防を期待できる抗不安作用を有するセントジョーンズウォート、抗酸化作用を有する松の樹皮抽出エキス、並びに血圧上昇抑制作用を有するＧＡＢＡ（γ−アミノ酪酸）などである。
本発明の食品組成物における、凍結乾燥した乳発酵産物の使用量としては、健康食品全重量に対して、１０〜４０重量％、好ましくは１０〜３５重量％、より好ましくは２０〜３０重量％である。本発明のナットウキナーゼとしては、市販のナットウキナーゼの重量として、食品組成物全重量に対して、５〜２５重量％、好ましくは５〜２０重量％、より好ましくは１０〜１５重量％である。
本発明の食品組成物における、凍結乾燥した乳発酵産物とナットウキナーゼの使用量は、その重量比で１：０．１〜２、好ましくは１：０．３〜１、より好ましくは約１：０．３〜０．８である。
前記した補助成分の使用量には特に制限はないが、食品組成物全重量に対して、０．１〜３５重量％、好ましくは０．２〜２５重量％、より好ましくは０．２〜２０重量％である。補助成分は添加する成分によってその使用量を調整することも必要である。
本発明の食品組成物は、前記した成分のほかに、食品として使用される増量剤、増粘剤、味覚調整剤、滑沢剤、崩壊剤などを添加することができる。また、必要に応じて色素により着色することもできる。
これらの添加成分としては、例えばマルチトール、結晶セルロース、増粘多糖類、馬鈴薯デンプン、米ヌカロウなどが挙げられる。
本発明の食品組成物は上述した成分を混合して製造することができる。混合はこれらの成分を一度に混合することができるが、数種類の成分を混合して得られた混合物を他の成分と混合してもよい。
本発明の食品組成物及びこれを用いた食品類の形状は粉末状であっても良いが、摂取を容易にするために好ましくは錠剤状または顆粒状である。更に好ましくは、コーティングされた錠剤状である。コーティング層によって納豆の臭いをさらに効果的に防止することができる。錠剤は摂取の妨げにならない範囲において如何なる形および大きさであっても良く、たとえば微小卵形または鼓形であってもよい。
コーティング剤としては、酵母細胞壁、ゼラチン、グリセリン、デンプン、セルロース等の既存材料を適宜用いることができ、好ましくは酵母細胞壁である。
本発明の食品組成物は、主成分に加えて複合ビタミン剤、有胞子性乳酸菌、カルシウム剤、オリゴ糖、食物繊維、ホスファチジルセリンなどの補助成分、および増量剤などの錠剤化成分、並びにコーティング剤からなる群から各成分を必要に応じて適宜選択することができる。脳細胞活性化作用を有することから、少なくともホスファチジルセリン（ＰＳと略記）を添加したものが好ましい。
本発明の食品組成物の一粒子中の成分と組成の一例を下記の表１に示す。
本発明の食品組成物は上述したとおり、凍結乾燥した乳発酵産物、例えば凍結乾燥ケフィアとナットウキナーゼを主成分とするので、下記の効果を奏することができる。
まず、ナットウキナーゼは、納豆菌が産生する極めて強いフィブリン分解能を有する血栓溶解酵素である。すなわち、乳発酵産物とナットウキナーゼが共に抗血栓作用を有するので、相乗作用による更なる効果がある。従って本発明の食品組成物は、心臓病（心筋梗塞・狭心症等）、脳血管疾患（脳梗塞・脳血栓等）のような日本人の死亡原因の３１％（平成７年、厚生省統計）を占める血栓症の治療と予防に十分な効果があると考えられる。ナットウキナーゼは、従来使用されてきた血栓溶解剤（ウロキナーゼ・ＴＰＡ）がいずれも血中半減期が４〜２０分と極めて短いのに対して４〜１２時間と長時間である。従ってナットウキナーゼは血栓溶解作用を長時間にわたって持続することができる。更に血栓症は老人性痴呆症の一つの原因であることから、ナットウキナーゼは血栓型痴呆症の予防にも効果があると考えられる。しかも、ナットウキナーゼは日本古来の代表的発酵食品である納豆中に見出された酵素であるので、大量生産が可能で、他の薬品と比較して非常に安価で提供することができ、かつ古来から食品として経口摂取されている納豆の安全性が十分に保証されているなどの優れた特徴を有している。
一方、乳発酵産物の保健効果については、古くから整腸作用を有することが知られており、また消化管を中心とする感染防御の関点から、そして癌細胞抑制効果との関連で免疫賦活作用が示唆されている。更に乳発酵産物の摂取が癌の発生を抑制することが示唆され、抗腫瘍活性が報告されている。更にまた乳発酵産物の投与によって血小板やフィブリノーゲンが増加し、一方、フィブリンの分解によって形成されるフィブリン分解産物が減少して正常値に近づくことが認められている。すなわち、フィブリン分解産物の減少は、フィブリンの更なる減少を意味し、血栓は血液凝固により生じたフィブリンが主体であるので、血流が順調になり血流阻害が解消されて抗血栓作用が高められ、血圧降下作用も期待できる。
また、本発明の食品組成物は、好ましくは錠剤化され、かつその表面がコーティングされているので、取り扱いと摂取が容易であり、かつ納豆の臭気への違和感を解消することができる。加えて本発明の食品組成物においては、補助成分の配合とその種類の選択によって、主成分のみで充足しえない補助成分固有の効果を期待することができる。すなわち、有胞子乳酸菌は安定性が高く、乳酸菌生成能力も優れているので、確実に腸管に到達し、活発な整腸作用が見込まれる。カルシウム剤はカルシウム補強作用を、複合ビタミン剤は特定ビタミン強化作用を有する。
以下に、実施例により本発明をより詳細に説明するが、本発明はこれらの実施例に限定されるものではない。
実施例
実施例１
ケフィア粉末２５．０ｇ、ナットウキナーゼ１０．５ｇ、及び錠剤化材料を混合、錠剤化し、未コーティングの微小鼓状の錠剤を得た。得られた錠剤は、平均重量０．３００ｇであった。これに酵母細胞壁コーティング剤により被覆を施し、本発明の健康食品を得た。コーティングした錠剤は０．３１０ｇ（平均重量）であった。この錠剤を１日３粒投与した。
実施例２
ケフィア粉末２０．０ｇ、ナットウキナーゼ１０．５ｇ、高麗人参１０ｇ、黒酢８ｇ、いちょう葉５ｇ、ホスファチジルセリン５ｇ、及びカプセル化材料を混合し、平均重量０．３００ｇのカプセルを得た。このカプセルを１日３カプセル投与した。
実施例３
ケフィア粉末２８．０ｇ、ナットウキナーゼ１０．５ｇ、複合ビタミン剤（粉末）２．５ｇ、有胞子性乳酸菌０．２ｇ、カルシウム剤（ミルクＣａ）４．８ｇ、及び錠剤化材料マルチトール（増量剤）２８．５ｇ、錠剤化材料８．５ｇを混合し、混練物を得た。次に、この混練物から造粒工程において微小鼓状の未コーティング錠剤を得た。得られた錠剤は、平均重量０．３５０ｇであり、酵母細胞壁コーティング剤により被覆を施し、本発明の健康食品を得た。コーティングした錠剤は０．３７１ｇ（平均重量）であった。この錠剤を１日３粒投与した。
試験例１
実施例３で製造したケフィア・ナットウキナーゼ錠（以下、ＫＫと略記することもある。）を、納豆及び乳製品のどちらかが苦手な人２０名（男性８名、女性１２名）に１週間服用してもらい、その効果を調査した。
＜調査の結果＞
１．食べるのに抵抗はありましたか？
はい ０名 （０％）
いいえ １９名（９５％）
どちらでもない １名 （５％）
２．飲み終えて、体に変化はありましたか。
お腹の調子がよくなった。 ８名（４０％）
肩こりがよくなった。 ３名（１５％）
よく眠れるようになった。 ２名（１０％）
つかれにくくなった。 １名 （５％）
特に変化はない。 ５名（２５％）
途中で飲むことを止めた。 １名 （５％）
この結果、本発明の食品組成物は、納豆や乳製品が苦手な人においても摂取できる食品であり、納豆や乳製品に含有されている健康上好ましい成分を容易に摂取することができる食品であることがわかった。
また、調査が１週間という短い期間であったことから、特に変化はないと回答した人が２５％であったが、１週間という短い期間にもかかわらず「お腹の調子がよくなった」という人が２５％おり、「肩こりがよくなった」という人が１５％おり、「よく眠れるようになった」という人が１０％いたことは、本発明の食品組成物が優れた作用効果を有するものであることを示している。
試験例２
実施例３で調製したケフィア・ナットウキナーゼ錠の摂取による血液流動性向上効果について、Ｍｉｃｒｏ Ｃｈａｎｎｅｌ Ａｒｒａｙ Ｆｌｏｗ Ａｎａｌｙｚｅｒ（ＭＣ−ＦＡＮ）を用いて血小板凝集の抑制と赤血球変形能の改善、および血中脂質量を指標にした効果を試験した。
Ｉ．試験方法
（１）被験者
男性は女性よりも血液の流動性が一般的に低く、年齢が高くなるにつれてその流動性が低くなる傾向にあることが予試験の結果から明らかである。そこで、今回の臨床試験においては、被験者に試験の意義、被検体の安全性について十分な説明を行った上で、４０代以上の日本人男性のボランティア８名（Ｎ−１〜８）に協力してもらった。
（２）ケフィア・ナットウキナーゼ錠の摂取
被験者には測定１週間前より納豆、ピーマン、南京豆（ピーナッツ）、玉葱、梅など、血液の流動性に影響を及ぼすといわれている食材の摂取を控えてもらった。試験当日の朝食は水以外を取らず、午前９時から１０時までに医師の立ち会いの下、採血後の飲食も水以外は控えてもらった。
採血は医師により行われ、採血後に本発明による通常の２倍量である６錠のケフィア・ナットウキナーゼ錠を白湯で摂取してもらった。
（３）採血とヘパリン化血液の調製
被験者の上腕静脈より７〜８ｍＬの血液を採取し、その１．９ｍＬをヘパリン溶液１０００単位／ｍＬの０．１ｍＬを前もって分注しておいたポリエチレン製測定用試験管に分取し、全血の流動性測定用血液とした。残りの血液４ｍＬは血液検査用に用いた。
（４）血液流動性の測定
血液の流動性はＫｉｋｕｃｈｉらの方法に従って測定した。すなわち、２０ｃｍ水柱差でＭＣ−ＦＡＮに組み込まれたマイクロチャンネルアレイ（Ｂｌｏｏｄｙ ６−７：日立原町電子工業社製）を全血１００μｌが通過する時間を計測した。血液通過時間は測定する直前に計測される生理食塩液１００μｌの通過時間を１２秒として換算し、次式により算出した。
血液通過時間×１２秒／生理食塩液通過時間
（５）血液流動性試験
（ｉ）１回摂取による効果
ケフィア・ナットウキナーゼ錠に摂取前と摂取２時間後に採取した血液の流動性を比較し、１回摂取による効果を判定した。今回、血液凝固阻止剤としてヘパリンを用いた。ヘパリンは血液中の凝固因子フィブリノーゲンをフィブリンに変換するトロンビンの活性を阻害する。しかし、血小板凝集に対するその効果は弱いといわれている。よって、採取された血液に含まれる血小板は凝集しやすい状態にあるといえる。
そこで、全血の流動性と血小板凝集に及ぼすケフィア・ナットウキナーゼ錠の影響をみる目的で、採血の直後（実際には採血後３分）とその１０分後（血小板凝集しやすい血液性状にある血液が凝集を起こす時間）に測定した。
（ｉｉ）連日摂取による効果
上記の試験日を０日目とし、被験者にはそれ以後１週間、毎食前３回、通常の２倍量である６錠のケフィア・ナットウキナーゼ錠を白湯で摂取してもらい、７日後に再度全血の流動性を測定した。
なお、この期間中の食事は先にあげた食材以外のものを普段どおりに摂ってもらい、生活様式も極力普段どおりにしてもらった。
（ｉｉｉ）血液検査
血液検査は試験開始日と最終日に血液の流動性や血小板凝集に影響を及ぼすといわれている総コレステロール、ＨＤＬコレステロール、ＬＤＬコレステロール、中性脂肪、遊離脂肪酸、Ｈｔ値、赤血球数、血小板数および白血球数を測定した。
ＩＩ．試験結果
（１）被験者の血液性状と今回の測定方法の評価
上記の技術による血液の流動性を測定する方法は、比較的簡単で再現性にも優れている。しかし、採血時に何らかの刺激が加わると、血液は急激に凝固する性質があり、またこの反応は連鎖反応でもある。これはヒトの生体防御システムのひとつで、出血した時にこの反応が起こらないと止血できず、死に至ることになる。
今回の試験には８名の被験者に協力をしてもらったが、採血時の不手際で２例に凝固反応がみられた。これらの被験者についてはすべてのデータを削除し、６名のデータをもってケフィア・ナットウキナーゼ錠の有効性を判定した。
まず、採血３分後における摂取前の全血の流動性を、１００μＬの血液が通過する時間として第１図に示した。最も短いヒトで３４．２秒で、最も長いヒトでも６０．４秒で、文献値からみてもこれらの被験者の値は健常といえる。ところが、採血後１０分に再度同血液を測定したところ、被験者Ｎ−５及びＮ−６から採血した血液の全血通過時間は、それぞれ、４６．１秒から８４．１秒へ、４５．８秒から１２０．０秒へと変化し、モニター上に血小板凝集が観察された。すなわち、被験者Ｎ−５、Ｎ−６の血液は血小板易凝集状態といえる。測定時間を２段階方式にすることによって、このような極めて価値ある被験者についての情報を見出すことができた。
（ｉ）ケフィア・ナットウキナーゼ錠の１回摂取による効果
前値測定直後に通常量の２倍量のケフィア・ナットウキナーゼ錠を摂取してもらい、その２時間後に再度、全血の通過時間を採血後３分と１０分に測定した。
採血後３分の測定においては、６例中１例を除き５例において全血の通過時間が短縮された。その結果を第１図に示す。
採血後１０分の測定においては、血小板が易凝集状態にある被験者のＮ−５、Ｎ−６の全血通過時間が顕著に短縮され、モニター上にも血小板凝集が観察されなかった。その結果を第２図に示す。
これらの結果から、ケフィア・ナットウキナーゼ錠は、血液をサラサラにする効果、いわゆる血液流動性向上効果があり、その作用機序の一つとして血小板凝集抑制作用が示唆された。
（ｉｉ）ケフィア・ナットウキナーゼ錠の連日摂取による効果
上述のようにケフィア・ナットウキナーゼ錠を７日間連日摂ってもらい、再度、全血の通過時間を測定した。その結果、６例中４例の全血通過時間が短縮し、１例は変化せず、１例（Ｎ−８）が延長した。その結果を第３図に示す。さらに、摂取前、摂取後２時間の測定結果と併せて、第４図に示す。
被験者Ｎ−８は、測定前にセットの準備、医師と被験者間の指示連絡、他の被験者へのケアなどに関わっていたため、これがストレッサーになり、全血の通過時間が延長されたことも考えられる。
また、血小板が易凝集状態にある被験者Ｎ−５及びＮ−６について、摂取前、摂取後２時間、摂取後１週間の測定結果を併せて、第５図に示す。
（ｉｉｉ）血液検査
全血の流動性や血小板凝集に及ぼす血清成分や血球成分を測定し、その結果を下記の表２に示した。１週間の連日摂取により中性脂肪量が低下し、遊離脂肪酸量が増加する傾向がみられた。この結果より、脂質代謝異常への有効性が期待できる。
以上の結果から、ケフィア・ナットウキナーゼ錠には全血の流動性を向上させる効果、血小板凝集抑制効果が示唆された。特に、血小板が易凝集状態にあるヒトの全血通過時間を短縮させたことは極めて価値のある効果といえる。
今後は血液が凝固した時に積極的にそれを早く溶解させる線溶系に対する効果を検討する必要があると思われる。
産業上の利用可能性
本発明の食品組成物は上述したとおり、納豆由来のナットウキナーゼと凍結乾燥した乳発酵産物、例えば凍結乾燥ケフィアを主成分とするので、下記の効果を奏することができる。
まず、ナットウキナーゼは、納豆菌が産生する極めて強いフィブリン分解能を有する血栓溶解酵素であり、乳発酵産物と共に抗血栓作用を有するので、相乗作用による更なる効果があり、血栓症の治療と予防に十分な効果があると考えられる。またナットウキナーゼは、血栓型痴呆症の予防にも効果があると考えられる。
しかもナットウキナーゼは日本古来の代表的発酵食品である納豆中に見出された酵素であるので、大量生産が可能で、他の薬品と比較して安価に提供することができ、かつ古来からの納豆の経口摂取により安全性が十分に保証されているなどの優れた特徴を有している。
一方、乳発酵産物の保健効果については、古くから整腸作用を有することが知られており、また消化管を中心とする感染防御の関点から、そして癌細胞抑制効果との関連で免疫賦活作用が示唆されている。更に乳発酵産物の摂取が癌の発生を抑制することが示唆され、抗腫瘍活性が報告されている。更にまた乳発酵産物の投与によって血小板やフィブリノーゲンが増加し、一方、フィブリンの分解によって形成されるフィブリン分解産物が減少して正常値に近づくことが認められている。すなわち、フィブリン分解産物の減少は、フィブリンの更なる減少を意味し、血栓は血液凝固により生じたフィブリンが主体であるので、血流が順調になり血流阻害が解消されて抗血栓作用が高められ、血圧降下作用も期待できる。
さらに、本発明の食品組成物は、他の各種補助成分を含有させることにより、抗血栓作用のみならず、血液流動性向上作用、血小板凝集抑制作用、及び脂質代謝改善作用など種々の保健効果を期待できる機能性食品として利用が可能である。
【図面の簡単な説明】
第１図は、試験例２の結果を示す図である。ケフィア・ナットウキナーゼ錠を１回摂取した場合の血液流動性向上効果を示す。
第２図は、試験例２の結果を示す図である。ケフィア・ナットウキナーゼ錠を１回摂取した場合の血液流動性向上効果を示す。
第３図は、試験例２の結果を示す図である。ケフィア・ナットウキナーゼ錠を７日間摂取した場合の血液流動性向上効果を示す。
第４図は、試験例２の結果を示す図である。ケフィア・ナットウキナーゼ錠による血液流動性向上効果を示す。
第５図は、試験例２の結果を示す図である。被験者のうちＮ−５及びＮ−６についての血液流動性向上効果を示す。 TECHNICAL FIELD The present invention relates to a health food derived from natto that has been in the Japanese diet for a long time. More specifically, it relates to a food composition containing a fermented animal milk product that has attracted attention for its health effects and a nattokinase derived from natto that has long been adopted in the Japanese diet. The present invention relates to a functional food which has a fluidity improving effect, a platelet aggregation suppressing effect, and a lipid metabolism improving effect, and is expected to have excellent effects in treating and preventing thrombosis.
BACKGROUND ART In recent years, in view of growing interest in health, in addition to the primary function of foods, which has a conventional function of maintaining life, and the secondary function of taste, the tertiary function of rhythm regulation of living organisms Various studies are also being conducted on physical condition regulating functions for maintaining health, such as protection, disease prevention and recovery, and aging prevention. Apart from drugs intended for symptomatic treatment, the incorporation of health or functional foods with enhanced tertiary functions to maintain health more aggressively into daily life is a concern for health. With increasing demand, medical expenses are expected to be restrained from increasing. In particular, diversification of lifestyles, changes in eating habits, and the like, further research from various fields is required for the preventive effects of such health foods or functional foods on lifestyle-related diseases and various chronic diseases. .
Functional foods are generally foods that are produced by new technology using ordinary foods and the like as raw materials and components, and that have more specific health effects than healthy foods that can be consumed on a daily basis. As an example, foods using sweeteners that do not easily cause tooth decay are on the market. These are not raw materials and materials that need to be specially prepared, and many are developed and manufactured from foods that are consumed or used traditionally.
Under such circumstances, health foods or functional foods have a wide range of needs, and more specific effects are also required.
For example, there is a tendency for functional foods to seek an effect of improving blood fluidity, which is generally referred to as an “effect of making blood smooth”. Factors governing blood fluidity involve vascular problems and the function of blood components. If the inner diameter of the blood vessel becomes narrow due to arteriosclerosis, blood flow becomes worse, and if the lipid level in the blood increases, blood viscosity increases, platelet aggregation also increases, and when blood clots form in blood vessels, Thrombolytic ability is reduced and blood flow is impaired. In addition, in the blood cell component, red blood cells having a larger diameter than capillaries pass through the capillaries so that they change their shape flexibly to give oxygen to vascular endothelial cells, receive Co 2 and circulate to the lungs through veins. are doing. Such erythrocyte flexibility is called erythrocyte deformability, and this function is exacerbated by lifestyle-related diseases, chronic diseases, stress, etc., and the microcirculation function is reduced.
As a specific food example, natto is a food that has been used and loved in Japan for a long time, and is a fermented food produced by Bacillus subtilis natto classified as a kind of Bacillus subtilis. As a traditional health food in Japan, "vegetable cheeses" are introduced in Europe and the United States. In recent years, it has been reported that natto contains an enzyme called nattokinase [nattokinase]. This nattokinase is easily purified from natto by a combination of extraction, salting-out, chromatography, gel filtration, etc., is a white crystalline powder, has a natto smell, is colorless and transparent, and has an aqueous solution of pH 6-12. It is known that it is stable against heating up to 60 ° C. in a basic aqueous solution. In addition, its amino acid sequence has also been determined, and it is known that the polypeptide is a single-chain polypeptide composed of 275 amino acid residues having no SS bond. Its molecular weight by gel filtration is 20,000 ± 5,000.
In terms of sustainability, nattokinase has an action time of 4 to 12 hours, which is longer than that of urokinase.
Nattokinase contained in natto not only has the unique texture of natto, but this enzyme is the same serine protease enzyme as thrombolytic enzyme urokinase and tissue plasminogen activator (TPA). It has a strong thrombolytic ability, and has also been confirmed to have an indirect effect of increasing the amount of TPA in blood.
As described above, various favorable effects of nattokinase on health have been reported. Nattokinase has a peculiar odor of natto, and if it is used as it is as a food, many nattokinases are required. There was a problem.
In addition, consumption of fermented animal milk products such as yogurt and cheese has been increasing due to increased interest in the health benefits of the food products, and various foods such as confectionery based on fermented animal milk products have been developed. Have been. In particular, it has been reported that there are many people who live long in ethnic groups who consume a large amount of fermented animal milk products, and that the incidence of cancer and the like is low, and fermented animal milk products as health foods have attracted attention. . In recent years, it has also been found to have a blood pressure lowering effect.
However, it is inherently unfriendly to Japanese people who have a basic diet of rice, especially elderly people.
DISCLOSURE OF THE INVENTION Although the present invention has attracted attention for its health effects, there are still people who are not good at combining milk fermented products and natto so that the elderly or young people, anyone in any region, can easily It is intended to provide a food composition which can be ingested and enjoy their health effects.
Further, the present invention provides a food composition in which nattokinase can be easily taken by improving the peculiar smell and taste of nattokinase.
The present inventors were examining a health food having both the effect of natto and the effect of fermented animal milk, and found that a food composition containing both natto, a Japanese-style ingredient, and fermented animal milk, a Western-style ingredient Has surprisingly found that it is possible to improve the peculiar smell and taste of nattokinase and to obtain a food that can sufficiently bring out the effects of both.
That is, the present invention relates to a food composition comprising a freeze-dried fermented milk product, nattokinase, and a carrier usable for food. In addition, the present invention relates to a food composition comprising a freeze-dried milk fermented product and nattokinase further containing an auxiliary component such as phosphatidylserine, a Korean participant product, or the like. Furthermore, the present invention relates to a functional food containing these components, which has an antithrombotic effect, a blood fluidity improving effect, a platelet aggregation suppressing effect, and a lipid metabolism improving effect.
BEST MODE FOR CARRYING OUT THE INVENTION The freeze-dried milk-fermented product in the food composition of the present invention is animal milk, that is, kefir or yogurt obtained by fermenting milk of cows, horses, sheep, goats and the like. , Coumis, Lassie, etc., and can be produced by methods known in the art. Preferably, it is a freeze-dried product of kefir, which is a product obtained by adding kefir grains to milk and fermenting (hereinafter, abbreviated as kefir), and its production method is described in, for example, JP-A-62-83842. Which is in the form of a white to pale yellowish white powder.
Next, the nattokinase (nattokinase: nattokinase) in the present invention will be described. This nattokinase is easily produced from natto (natto), a traditional fermented soybean food in Japan, by a combination of operations such as extraction, salting out, chromatography, and gel filtration, and commercially available products are also known. It has white crystalline powder and natto odor, and its aqueous solution is colorless and transparent, and is stable to heating up to 60 ° C in a basic aqueous solution having a pH of 6 to 12. It is the same serine enzyme as thrombolytic enzyme urokinase, tissue plasminogen activator (TPA), etc., its amino acid sequence has been determined, and it has a single-chain structure consisting of 275 residues without any SS bond. Characteristically, it is a polypeptide. The molecular weight by gel filtration is 20,000 ± 5,000 and the average activity is about 40 CU (plasmin units) / g. In addition to having a strong thrombolytic ability, an indirect effect of increasing the amount of TPA in blood has been confirmed. Nattokinase is inexpensive, has a long-lasting action, and has recently attracted attention for its efficacy against infectious diseases such as O-157.
As the nattokinase of the present invention, a commercially available nattokinase can be used as it is, and it is not always necessary to use a sufficiently purified nattokinase, as long as it contains nattokinase and can be used as food. There is no particular limitation. For example, any nattokinase containing nattokinase, such as natto extract or a processed product thereof, can be used as the nattokinase of the present invention.
The carrier in the food composition of the present invention can be used for foods and does not have a particular adverse effect on the flavor of the food composition of the present invention, but has a favorable effect on the health effects of nattokinase and milk fermented products. There is no particular limitation as long as it is a thing.
The auxiliary component in the food composition of the present invention is a food material used as a food or an extract thereof, which does not have a particular adverse effect on the flavor of the health food of the present invention, and has a health-related effect on nattokinase and fermented milk products. There is no particular limitation as long as it has a favorable effect on the function and effect of the present invention. Preferred auxiliary components include phospholipids such as phosphatidylserine, ginseng and the like.
Phosphatidylserine (PS) is a type of phospholipid, and it is said that it can improve brain functions such as learning ability, memory ability, thinking ability, cognitive ability against early stage Alzheimer's disease and memory deterioration due to aging. It is also expected to have an effect of improving Parkinson's disease and depression. In other words, PS is thought to have the effect of promoting the uptake of nutrients into cells, activating information transmission between nerve cells, and promoting the production of neurotransmitters, and is expected to be effective in treating Alzheimer-type dementia. You.
Ginseng has long been known as a component of health foods and herbal medicines, and may have effects such as hypoglycemic action, improvement of adrenal cortex function, improvement of myocardial function, improvement of metabolism, and improvement of cholesterol. Are known. For ginseng, ginseng-participated products, for example, extracts, dried products, powders and the like can be used.
Furthermore, as other preferred auxiliary components in the food composition of the present invention, various vitamins, calcium agents, lactic acid bacteria, oligosaccharides, dietary fiber, mumefural-containing plum extract, black vinegar and the like, which are food ingredients or extracts thereof used as foods Is mentioned.
Oligosaccharides are monosaccharides, such as glucose, fructose or galactose, having 2 to 10 glycoside linkages. Commercial products are already known, and lactic acid bacteria such as bifidobacteria and lactic acid bacteria, which are useful bacteria in the intestine, and fecalis. It is a growth factor that serves as a nutrient for bacteria. Therefore, useful intestinal bacteria can proliferate, and a favorable intestinal environment in which useful bacteria predominate can be created.
Dietary fiber is a fiber that is often contained in vegetable foods such as okara, dried shiitake, dried hijiki, jellyfish, laver, and soybeans. In the past, these components hindered the digestion and absorption of nutrients and were neglected as indigestible components that did not become an energy source. However, in recent years, attention has been paid to their intestinal effects and improved bowel movement.
Since spore-forming lactic acid bacteria have high stability and excellent ability to produce lactic acid bacteria, they reach the intestinal tract with certainty and are expected to have an active intestinal action. A calcium agent has a calcium reinforcing effect, and a complex vitamin agent has a function of enhancing a specific vitamin.
Mumefural-containing ume extract has long been known to have medicinal properties, and is known to have effects such as recovery from fatigue, antibacterial activity, anti-inflammation, and activation of digestive organs. Its components are diverse such as minerals, catechins and amino acids. In recent years, in particular, mumefural produced by heating the ingredients in the process of producing plum extract from raw plum has been found to have an effect of inhibiting platelet aggregation, and other components contained in plum extract Attention has been paid to the effect of improving blood flow due to the synergistic effect with the above.
Black vinegar is a type of vinegar produced from rice, which improves cholesterol and neutral fats (improves lipid metabolism), improves blood flow (improves erythrocyte deformability), anti-allergic effect, lowers blood pressure, It is known to have a hypoglycemic action, a liver activating action, an antioxidant action, and the like. However, in order to fully enjoy the health effects of nattokinase, it is preferable to carry out a process such as microencapsulation before adding it to the food composition. As the black vinegar, black vinegar obtained by using rice koji, steamed rice, and groundwater as raw materials and three fermentations of saccharification, alcohol fermentation, and acetic acid fermentation have naturally progressed is preferable.
Furthermore, the following food materials or extracts thereof used as foods can also be mentioned as auxiliary components in the food composition of the present invention. That is, onion extract having a fibrinolytic activity and a lipid lowering effect, peppers and peanuts having a blood flow improving effect, ginkgo leaves and tomatoes having a blood flow improving effect, CoQ10 (supplementary) having an antioxidant effect and a heart disease preventing effect. Enzyme Q10), astaxanthin having an antioxidant effect, tocotrienol having an antioxidant effect and an atherosclerosis-improving effect, St. John's wort having an anti-anxiety effect that can be expected to prevent heart disease, pine bark extract having an antioxidant effect, and GABA (γ-aminobutyric acid), which has a blood pressure elevation inhibitory effect, and the like.
The amount of the freeze-dried milk fermented product in the food composition of the present invention is 10 to 40% by weight, preferably 10 to 35% by weight, more preferably 20 to 30% by weight, based on the total weight of the health food. It is. The nattokinase of the present invention is 5 to 25% by weight, preferably 5 to 20% by weight, more preferably 10 to 15% by weight, based on the total weight of the food composition, as the weight of a commercially available nattokinase.
In the food composition of the present invention, the lyophilized milk fermented product and nattokinase are used in a weight ratio of 1: 0.1 to 2, preferably 1: 0.3 to 1, more preferably about 1: 0. 0.3 to 0.8.
The amount of the auxiliary component is not particularly limited, but is 0.1 to 35% by weight, preferably 0.2 to 25% by weight, more preferably 0.2 to 20% by weight based on the total weight of the food composition. % By weight. It is necessary to adjust the amount of the auxiliary component to be used depending on the component to be added.
The food composition of the present invention may contain, in addition to the components described above, extenders, thickeners, taste modifiers, lubricants, disintegrants, and the like used as foods. Moreover, it can also be colored with a pigment as needed.
These additional components include, for example, maltitol, crystalline cellulose, thickening polysaccharide, potato starch, rice bran and the like.
The food composition of the present invention can be produced by mixing the above-mentioned components. In mixing, these components can be mixed at once, but a mixture obtained by mixing several types of components may be mixed with other components.
The food composition of the present invention and foods using the same may be in the form of powder, but preferably in the form of tablets or granules for easy ingestion. More preferably, it is in the form of a coated tablet. The odor of natto can be more effectively prevented by the coating layer. Tablets may be of any shape and size as long as they do not interfere with consumption, for example, they may be micro-oval or drum-shaped.
Existing materials such as yeast cell walls, gelatin, glycerin, starch, and cellulose can be used as appropriate as the coating agent, and yeast cell walls are preferred.
The food composition of the present invention comprises, in addition to the main components, multivitamin preparations, spore-forming lactic acid bacteria, calcium preparations, oligosaccharides, dietary fiber, auxiliary components such as phosphatidylserine, and tableting components such as bulking agents, and coating agents. Each component can be appropriately selected from the group consisting of It is preferable to add at least phosphatidylserine (abbreviated as PS) since it has a brain cell activating action.
Table 1 below shows an example of components and compositions in one particle of the food composition of the present invention.
As described above, the food composition of the present invention contains a freeze-dried milk fermentation product, for example, freeze-dried kefir and nattokinase as main components, and thus can exert the following effects.
First, nattokinase is a thrombolytic enzyme produced by Bacillus natto having an extremely strong fibrin degrading ability. That is, since both the fermented milk product and the nattokinase have an antithrombotic effect, there is a further effect due to a synergistic effect. Therefore, the food composition of the present invention accounts for 31% of Japanese death causes such as heart disease (myocardial infarction, angina pectoris, etc.) and cerebrovascular disease (cerebral infarction, cerebral thrombosis, etc.) (1995, Ministry of Health and Welfare statistics). It is thought that it has a sufficient effect on the treatment and prevention of thrombosis, which accounts for. Nattokinase has a long half-life in blood of 4 to 20 minutes, whereas the conventionally used thrombolytic agent (urokinase / TPA) has an extremely short half-life of 4 to 20 minutes. Therefore, nattokinase can maintain the thrombolytic action for a long time. Furthermore, since thrombosis is one of the causes of senile dementia, nattokinase is considered to be also effective in preventing thrombotic dementia. Moreover, since nattokinase is an enzyme found in natto, a typical fermented food from ancient Japan, it can be mass-produced and can be provided at a very low price compared to other chemicals. Natto, which is orally ingested as a food product, has excellent characteristics such as sufficient safety.
On the other hand, the health effects of milk fermented products have long been known to have an intestinal activity, and they also have immunostimulatory effects in terms of protection of infection, mainly in the gastrointestinal tract, and in relation to cancer cell inhibitory effects. An effect has been suggested. Furthermore, it has been suggested that intake of milk fermentation products suppresses the occurrence of cancer, and antitumor activity has been reported. Furthermore, it has been observed that administration of a milk fermentation product increases platelets and fibrinogen, while reducing fibrin degradation products formed by fibrin degradation approaches normal values. In other words, a decrease in fibrin degradation products means a further decrease in fibrin, and blood clots are mainly fibrin produced by blood coagulation, so that blood flow is smooth, blood flow inhibition is eliminated, and antithrombotic action is enhanced. It can also be expected to lower blood pressure.
Further, since the food composition of the present invention is preferably tableted and its surface is coated, it is easy to handle and ingest, and it is possible to eliminate the discomfort to the odor of natto. In addition, in the food composition of the present invention, it is possible to expect an effect peculiar to the auxiliary component, which cannot be satisfied only by the main component, by blending the auxiliary component and selecting its type. That is, since spore-forming lactic acid bacteria have high stability and excellent lactic acid bacteria-producing ability, they reliably reach the intestinal tract, and active intestinal regulation is expected. A calcium agent has a calcium reinforcing effect, and a complex vitamin agent has a specific vitamin enhancing effect.
Hereinafter, the present invention will be described in more detail with reference to Examples, but the present invention is not limited to these Examples.
Example Example 1
25.0 g of kefir powder, 10.5 g of nattokinase, and a tableting material were mixed and tableted to obtain an uncoated minute drum-shaped tablet. The resulting tablets had an average weight of 0.300 g. This was coated with a yeast cell wall coating agent to obtain the health food of the present invention. The coated tablets weighed 0.310 g (average weight). Three tablets were administered per day.
Example 2
20.0 g of kefir powder, 10.5 g of nattokinase, 10 g of ginseng, 8 g of black vinegar, 5 g of ginkgo leaf, 5 g of phosphatidylserine, and an encapsulating material were mixed to obtain a capsule having an average weight of 0.300 g. The capsules were administered three capsules a day.
Example 3
Kefir powder 28.0 g, nattokinase 10.5 g, complex vitamin preparation (powder) 2.5 g, spore-forming lactic acid bacterium 0.2 g, calcium preparation (milk Ca) 4.8 g, and tableting material maltitol (bulking agent) 28 0.5 g and a tableting material 8.5 g were mixed to obtain a kneaded product. Next, an uncoated tablet in the form of a small drum was obtained from the kneaded product in the granulation step. The obtained tablet had an average weight of 0.350 g and was coated with a yeast cell wall coating agent to obtain a health food of the present invention. The coated tablets weighed 0.371 g (average weight). Three tablets were administered per day.
Test example 1
Kefir nattokinase tablets (hereinafter sometimes abbreviated as KK) produced in Example 3 were taken for one week to 20 people (8 men and 12 women) who were not good at either natto or dairy products. We asked them to investigate their effects.
<Result of the survey>
1. Did you have any resistance to eating?
Yes 0 people (0%)
No 19 (95%)
Neither one person (5%)
2. Did you change your body after drinking?
My stomach is getting better. 8 (40%)
My stiff shoulders have improved. 3 (15%)
I can sleep well. 2 people (10%)
It became hard to be caught. 1 person (5%)
There is no particular change. 5 (25%)
Stopped drinking on the way. 1 person (5%)
As a result, the food composition of the present invention is a food that can be ingested even by those who are not good at natto and dairy products, and is a food that can easily ingest the health-friendly ingredients contained in natto and dairy products. I found it.
In addition, 25% of the respondents answered that there was no particular change because the survey was a short period of one week, but said that despite the short period of one week, "the stomach became better." 25% of the people, 15% said "I got better stiffness" and 10% said "I got better sleep" means that the food composition of the present invention has an excellent action effect It is a thing.
Test example 2
Regarding the blood fluidity improving effect by ingestion of the Kefir nattokinase tablet prepared in Example 3, the suppression of platelet aggregation, the improvement of erythrocyte deformability, and the blood lipid amount were measured using a Micro Channel Array Flow Analyzer (MC-FAN). The indexed effect was tested.
I. Test Method (1) It is clear from the results of the preliminary test that the blood flow of blood is generally lower in male subjects than in females, and the fluidity tends to decrease with age. Therefore, in this clinical trial, we explained the significance of the test and the safety of the subject to the subjects, and cooperated with eight Japanese male volunteers (N-1 to 8) in their 40s and over. I was asked to.
(2) Subjects taking Kefir Nattokinase Tablets have been asked to refrain from eating foods that are said to affect blood fluidity, such as natto, peppers, peanuts, onions, and plums, one week before the measurement. Was. On the day of the test, breakfast was taken except for water, and between 9 am and 10 am, a doctor was present to stop eating and drinking after blood sampling.
Blood collection was performed by a physician, and after blood collection, 6 kefir nattokinase tablets, twice the usual amount according to the present invention, were ingested with plain water.
(3) Blood collection and preparation of heparinized blood 7-8 mL of blood was collected from the brachial vein of the subject, and 1.9 mL of the measurement was made of polyethylene in which 0.1 mL of a 1000 unit / mL heparin solution was dispensed in advance. Was collected into test tubes for use as blood for measuring the fluidity of whole blood. The remaining 4 mL of blood was used for a blood test.
(4) Measurement of blood fluidity The blood fluidity was measured according to the method of Kikuchi et al. That is, the time required for 100 μl of whole blood to pass through a microchannel array (Bloody 6-7: manufactured by Hitachi Haramachi Electronics Co., Ltd.) incorporated in MC-FAN with a water column difference of 20 cm was measured. The blood transit time was calculated according to the following formula by converting the transit time of 100 μl of the physiological saline solution measured immediately before the measurement as 12 seconds.
Blood transit time × 12 seconds / physiological saline transit time (5) Blood fluidity test (i) Effect of single ingestion The fluidity of blood collected before and 2 hours after ingestion of Kefir Nattokinase tablets was compared. The effect of single ingestion was determined. This time, heparin was used as an anticoagulant. Heparin inhibits the activity of thrombin, which converts the blood clotting factor fibrinogen to fibrin. However, its effect on platelet aggregation is said to be weak. Therefore, it can be said that the platelets contained in the collected blood are in a state of being easily aggregated.
Therefore, in order to examine the effect of the Kefir Nattokinase tablet on the fluidity of whole blood and platelet aggregation, immediately after blood collection (actually 3 minutes after blood collection) and 10 minutes after that (blood having a blood property that easily causes platelet aggregation) (The time at which aggregation occurs).
(Ii) Effect of Daily Intake The above test day was designated as day 0, and after that, the subjects were ingested 6 times the usual amount of 6 tablets of kefir nattokinase tablet with plain water three times before meals for one week thereafter for one week. After 7 days, the fluidity of whole blood was measured again.
In addition, during this period, they were asked to eat food other than the above-mentioned ingredients as usual, and to have their lifestyle as normal as possible.
(Iii) Blood test The blood test is said to affect blood fluidity and platelet aggregation on the first day and the last day of the test. Total cholesterol, HDL cholesterol, LDL cholesterol, neutral fat, free fatty acid, Ht value, erythrocyte The number, platelet count and white blood cell count were measured.
II. Test Results (1) Evaluation of Blood Properties of Subject and Measurement Method This time The method for measuring blood fluidity by the above technique is relatively simple and has excellent reproducibility. However, when a certain stimulus is applied during blood collection, the blood has a property of rapidly coagulating, and this reaction is also a chain reaction. This is one of the human body defense systems, and if this reaction does not occur when bleeding, it will not be able to stop bleeding and will result in death.
Eight subjects cooperated in this study, but two had coagulation reactions due to inadequate blood sampling. For these subjects, all data were deleted, and the efficacy of Kefir Nattokinase tablets was determined based on the data of six subjects.
First, the fluidity of whole blood before ingestion 3 minutes after blood collection was shown in FIG. 1 as the time for 100 μL of blood to pass. It is 34.2 seconds for the shortest human and 60.4 seconds for the longest human, and the values of these subjects can be said to be healthy from the literature values. However, when the same blood was measured again 10 minutes after the blood collection, the whole blood passage time of the blood collected from the subjects N-5 and N-6 was 45.8 seconds from 46.1 seconds, and 45.8 seconds respectively. From 12 seconds to 120.0 seconds, platelet aggregation was observed on the monitor. That is, it can be said that the blood of the subjects N-5 and N-6 is in a platelet-aggregated state. By using a two-stage measurement time, information about such extremely valuable subjects could be found.
(I) One time ingestion of the kefir nattokinase tablet immediately after the measurement of the pre-effect value, the patient was ingested twice the usual amount of the kefir nattokinase tablet, and two hours later, the passage time of the whole blood was again measured 3 hours after blood collection. Minutes and 10 minutes.
In the measurement 3 minutes after blood collection, the transit time of whole blood was shortened in 5 cases except 1 case out of 6 cases. The result is shown in FIG.
In the
These results suggest that Kefir nattokinase tablets have an effect of making blood smooth, a so-called blood fluidity improving effect, and one of the action mechanisms is a platelet aggregation inhibitory effect.
(Ii) Effect of daily intake of kefir nattokinase tablets As described above, kefir nattokinase tablets were taken daily for 7 days, and the transit time of whole blood was measured again. As a result, the whole blood transit time was shortened in four of the six cases, one case was unchanged, and one case (N-8) was prolonged. The results are shown in FIG. FIG. 4 shows the results before and two hours after ingestion.
Subject N-8 was involved in preparation of the set, communication of instructions between the doctor and the subject, care of other subjects, etc. before the measurement, so this became a stressor, and it was considered that the transit time of whole blood was extended. Can be
FIG. 5 also shows the measurement results of subjects N-5 and N-6 in which platelets are in an easily aggregated state before, 2 hours after, and 1 week after ingestion.
(Iii) Blood test Serum components and blood cell components affecting whole blood fluidity and platelet aggregation were measured. The results are shown in Table 2 below. The daily intake for one week tended to decrease the amount of neutral fat and increase the amount of free fatty acid. From these results, it can be expected to be effective for lipid metabolism disorders.
In the future, it will be necessary to study the effect on the fibrinolytic system, which actively dissolves blood when it has clotted.
Industrial applicability As described above, the food composition of the present invention contains nattokinase derived from natto and a freeze-dried milk fermentation product, for example, freeze-dried kefir, as described above. Can be.
First, nattokinase is a thrombolytic enzyme having an extremely strong fibrin degrading ability produced by Bacillus natto, and has an antithrombotic effect together with the milk fermentation product. It is thought that there is an effect. Nattokinase is also considered to be effective in preventing thrombotic dementia.
In addition, nattokinase is an enzyme found in natto, a typical fermented food from Japan since ancient times, so it can be mass-produced, can be provided at a lower cost than other chemicals, and It has excellent features such as its safety is sufficiently ensured by oral ingestion.
On the other hand, the health effects of milk fermented products have long been known to have an intestinal activity, and they also have immunostimulatory effects in terms of protection of infection, mainly in the gastrointestinal tract, and in relation to cancer cell inhibitory effects. An effect has been suggested. Furthermore, it has been suggested that intake of milk fermentation products suppresses the occurrence of cancer, and antitumor activity has been reported. Furthermore, it has been observed that administration of a milk fermentation product increases platelets and fibrinogen, while reducing fibrin degradation products formed by fibrin degradation approaches normal values. In other words, a decrease in fibrin degradation products means a further decrease in fibrin, and blood clots are mainly fibrin produced by blood coagulation, so that blood flow is smooth, blood flow inhibition is eliminated, and antithrombotic action is enhanced. It can also be expected to lower blood pressure.
Furthermore, the food composition of the present invention, by including other various auxiliary components, has not only an antithrombotic effect but also various health effects such as a blood fluidity improving effect, a platelet aggregation suppressing effect, and a lipid metabolism improving effect. It can be used as a functional food that can be expected.
[Brief description of the drawings]
FIG. 1 is a diagram showing the results of Test Example 2. The effect of improving blood fluidity when Kefir Nattokinase tablets are ingested once is shown.
FIG. 2 is a diagram showing the results of Test Example 2. The effect of improving blood fluidity when Kefir Nattokinase tablets are ingested once is shown.
FIG. 3 is a diagram showing the results of Test Example 2. The effect of improving blood fluidity when Kefir Nattokinase tablets are ingested for 7 days is shown.
FIG. 4 is a diagram showing the results of Test Example 2. The effect of improving blood fluidity by Kefir Nattokinase tablets is shown.
FIG. 5 is a diagram showing the results of Test Example 2. The blood fluidity improving effect of N-5 and N-6 among test subjects is shown.
Claims (11)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2001082366 | 2001-03-22 | ||
| JP2001082366 | 2001-03-22 | ||
| PCT/JP2002/002753 WO2002076240A1 (en) | 2001-03-22 | 2002-03-22 | Health foods containing natto kinase and fermented milk porducts |
Publications (2)
| Publication Number | Publication Date |
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| JPWO2002076240A1 true JPWO2002076240A1 (en) | 2004-07-08 |
| JP3572306B2 JP3572306B2 (en) | 2004-09-29 |
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| JP2002574765A Expired - Lifetime JP3572306B2 (en) | 2001-03-22 | 2002-03-22 | Health food containing nattokinase and fermented milk products |
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| Country | Link |
|---|---|
| US (1) | US20040105914A1 (en) |
| JP (1) | JP3572306B2 (en) |
| CN (1) | CN1250114C (en) |
| WO (1) | WO2002076240A1 (en) |
Families Citing this family (18)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1559421B1 (en) * | 2002-11-06 | 2016-07-27 | Kao Corporation | Blood circulation promoting agent |
| JP2005220025A (en) * | 2004-02-03 | 2005-08-18 | Kenko Tsusho Kk | Oral ingestion composition |
| JP2005312424A (en) * | 2004-04-30 | 2005-11-10 | Nippon Kefia Kk | Method for producing fermented product using kefir grain, and fermented product obtained by the same |
| JP2006151950A (en) * | 2004-11-05 | 2006-06-15 | Oto Corporation:Kk | Bacillus natto culture extract-containing preparation and method for preserving bacillus natto culture extract |
| WO2006137636A1 (en) * | 2004-12-29 | 2006-12-28 | Joo-Whan Park | Tablet type milk including sea grass and manufacturing method thereof |
| WO2007002572A2 (en) * | 2005-06-24 | 2007-01-04 | N-Zymeceuticals, Inc. | Nattokinase for reducing whole blood viscosity |
| CN101744048B (en) * | 2008-12-18 | 2013-04-24 | 上海诺金科生物科技有限公司 | Natto yoghourt and preparation method thereof |
| WO2010116425A1 (en) * | 2009-03-30 | 2010-10-14 | 日本ケフィア株式会社 | Inhibitor of premalignant lesion in colon, and prophylactic agent for colorectal cancer |
| CN101861908A (en) * | 2010-05-25 | 2010-10-20 | 曾新义 | Ice product additive prepared by natto and preparation method thereof |
| CN102488071A (en) * | 2011-12-01 | 2012-06-13 | 河北联合大学 | Natto kinases ice cream and manufacturing method thereof |
| KR101407607B1 (en) | 2012-08-24 | 2014-06-16 | 유대용 | Preparation Method of Fermented Ginseng with high content of highfunctional ginsenoside Rg3 using Kefir, Fermented Ginseng and Fermented Ginseng Concentrate thereby |
| CN103948915B (en) * | 2014-05-05 | 2016-06-22 | 德立唯（北京）生物科技有限公司 | A kind of natto kinase composition for antithrombotic and thrombolytic that can improve stability and oral curative effect |
| KR102098914B1 (en) * | 2016-11-29 | 2020-04-09 | 청미바이오(주) | Composition of anti-inflammatory or anti-oxidation containing natto and kefir fermented component |
| CN107375913A (en) * | 2017-09-11 | 2017-11-24 | 南京御匾国健生物科技有限公司 | A kind of thrombus dredging collateral medicine for loading Nattokinase and preparation method thereof |
| JP7423179B2 (en) * | 2017-12-28 | 2024-01-29 | 小林製薬株式会社 | Foods containing polyphenols |
| CN108308535A (en) * | 2018-03-22 | 2018-07-24 | 武汉虹辰远荣生物制品有限公司 | It is a kind of that there are the natto health-oriented products and preparation method thereof for improving brain neuroblastoma function |
| JP7207878B2 (en) * | 2018-06-27 | 2023-01-18 | 小林製薬株式会社 | Foods containing Nattokinase |
| JP7207877B2 (en) * | 2018-06-27 | 2023-01-18 | 小林製薬株式会社 | Foods containing Nattokinase |
Family Cites Families (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS4892558A (en) * | 1972-03-15 | 1973-11-30 | ||
| US4702923A (en) * | 1985-10-08 | 1987-10-27 | Sennosuke Tokumaru | Lyophilized kefir yoghurt health food |
| JPH09154535A (en) * | 1995-12-07 | 1997-06-17 | Sanwa Kagaku Kenkyusho Co Ltd | Natto (fermented soybean)-containing composition |
| WO1998043498A1 (en) * | 1997-04-01 | 1998-10-08 | Nichimo Co., Ltd. | Product comprising health-promotive ingredient and process for producing the same |
| JP3280247B2 (en) * | 1996-11-07 | 2002-04-30 | 長島 敬志 | Natto food |
| JPH1118712A (en) * | 1997-07-07 | 1999-01-26 | Yoshiteru Shimoide | Tableted and capsulated food containing material produced by bacillus natto |
| JP2000325019A (en) * | 1999-05-21 | 2000-11-28 | Masanori Shinozaki | Tea drink containing protease |
| JP3881494B2 (en) * | 2000-04-21 | 2007-02-14 | 株式会社日本生物科学研究所 | Natto bacteria culture extract |
-
2002
- 2002-03-22 CN CNB028070046A patent/CN1250114C/en not_active Expired - Fee Related
- 2002-03-22 US US10/472,843 patent/US20040105914A1/en not_active Abandoned
- 2002-03-22 WO PCT/JP2002/002753 patent/WO2002076240A1/en active Application Filing
- 2002-03-22 JP JP2002574765A patent/JP3572306B2/en not_active Expired - Lifetime
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| Publication number | Publication date |
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| CN1250114C (en) | 2006-04-12 |
| JP3572306B2 (en) | 2004-09-29 |
| US20040105914A1 (en) | 2004-06-03 |
| CN1498083A (en) | 2004-05-19 |
| WO2002076240A1 (en) | 2002-10-03 |
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